For Hydroxyurea in Pediatric Patients With Sickle Cell Anemia, the Earlier the Better?

Thursday, March 16, 2017

Intensifying hydroxyurea (HU) therapy is safe and effective in pediatric patients with sickle cell anemia (SCA), but starting HU at an earlier age appeared to only offer short-term benefits in hemoglobin levels, according to results from the prospective, observational HUSTLE (Hydroxyurea Study of Long-Term Effects) trial.

Christina Abrams, MD, of the Le Bonheur Children’s Hospital at the University of Tennessee, and colleagues collected data from 151 children with SCA who had not yet completed the physiologic decline of fetal hemoglobin (HbF) and replacement with sickle hemoglobin. Researchers compared hematologic parameters between children who began HU before 5 years of age (n=49) and those who began treatment at ≥5 years of age (n=102). All patients received a standard dose of 20 mg/kg per day, which was escalated over time.

“Similar relationships were observed [after patients received] the maximal tolerated dose of HU (28.8 mg/kg per day in younger patients and 24.7 mg/kg per day in older patients),” the authors reported.

Though treatment with HU led to long-term improvements in hematologic parameters (TABLE), there were no differences between the two age groups, even after escalation of HU. “For example, the young group had an average increase of 13.3 percent in HbF, compared [with] 13.4 percent in the older group (p=0.87),” they wrote.

After 5 years of therapy, hemoglobin levels were slightly higher in the older patients (9.5 g/dL vs. 8.7 g/dL; p=0.03), but HbF levels were similar between groups, as HbF declined at comparable levels with age in both groups (19.2% vs. 19.3%; p=0.7).

“Intensifying HU to the maximum tolerated dose in young children with SCA is safe and efficacious, providing stable long-term improvement in numerous hematologic parameters,” Dr. Abrams and co-authors concluded. “At young ages, there appears to be a short-term additive effect of HU to the elevated baseline HbF, but this is not sustained.”

The study’s findings are limited by the small patient population and the authors noted that future research should evaluate the clinical effect of intensifying HU in very young patients.